VCV000037768.59 - ClinVar

NM_000059.4(BRCA2):c.1889C>T (p.Thr630Ile)

Germline

Top reviewed classifications are shown here.

Submission summary:

28 submissions

27 submitters

8 conditions

Reviewed by expert panel

Benign

Aug 2015 by Evidence-based…

for Breast-ovarian cancer, familial 2

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000059.4(BRCA2):c.1889C>T (p.Thr630Ile)

Variation ID: 37768 Accession: VCV000037768.59

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 13q13.1 13: 32333367 (GRCh38) [ NCBI UCSC ] 13: 32907504 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 12, 2013	Oct 20, 2024	Aug 10, 2015

HGVS

Nucleotide	Protein	Molecular consequence
NM_000059.4:c.1889C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000050.3:p.Thr630Ile	missense
NC_000013.11:g.32333367C>T
NC_000013.10:g.32907504C>T
NG_012772.3:g.22888C>T
LRG_293:g.22888C>T
LRG_293t1:c.1889C>T	LRG_293p1:p.Thr630Ile
U43746.1:n.2117C>T

... more HGVS ... less HGVS

Protein change

T630I

Other names

p.T630I:ACA>ATA
2117C>T

Canonical SPDI

NC_000013.11:32333366:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

The Genome Aggregation Database (gnomAD) 0.00012

Trans-Omics for Precision Medicine (TOPMed) 0.00012

Exome Aggregation Consortium (ExAC) 0.00018

The Genome Aggregation Database (gnomAD), exomes 0.00021

Links

ClinGen: CA013740 dbSNP: rs80358479 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
BRCA2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	18969	19128

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Breast-ovarian cancer, familial, susceptibility to, 2	Benign (6)	reviewed by expert panel	Aug 10, 2015	RCV000031349.22
not provided	Benign/Likely benign (5)	criteria provided, multiple submitters, no conflicts	Jun 1, 2024	RCV000034433.41
Hereditary cancer-predisposing syndrome	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Jan 19, 2021	RCV000162511.14
not specified	Benign/Likely benign (7)	criteria provided, multiple submitters, no conflicts	Feb 6, 2024	RCV000193487.23
Breast and/or ovarian cancer	Likely benign (2)	criteria provided, single submitter	Apr 27, 2023	RCV000735526.10
Hereditary breast ovarian cancer syndrome	Benign (2)	criteria provided, multiple submitters, no conflicts	Jan 31, 2024	RCV001082203.15
Fanconi anemia complementation group D1	Uncertain significance (1)	criteria provided, single submitter	Jan 13, 2018	RCV001111739.12
BRCA2-related disorder	Benign (1)	no assertion criteria provided	Oct 3, 2019	RCV004532434.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Aug 10, 2015)	reviewed by expert panel (ENIGMA BRCA1/2 Classification Criteria (2015)) Method: curation	Breast-ovarian cancer, familial 2 Affected status: unknown Allele origin: germline	Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Accession: SCV000244427.1 First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015	Publications: PubMed (1) PubMed: 21990134 Other databases http://hci-exlovd.hci.utah.edu/v… http://hci-exlovd.hci.utah.edu/variants.php?select_db=BRCA2&action=search_all&search_Variant%2FDNA=c.1889C%3ET Comment: IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on … (more) IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000000121 (less)
Likely benign (Jul 17, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000246806.1 First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015
Uncertain significance (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Fanconi anemia complementation group D1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001269324.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
Uncertain significance (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001269323.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
Benign (Mar 09, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: unknown Allele origin: germline	Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. Accession: SCV004014921.1 First in ClinVar: Jul 22, 2023 Last updated: Jul 22, 2023
Benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000071930.16 First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024
Likely benign (Mar 21, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000602820.3 First in ClinVar: Sep 28, 2017 Last updated: Feb 20, 2024
Benign (Jun 12, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV004848657.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024	Comment: The p.Thr630Ile variant in BRCA2 is classified as benign because it has been identified in 0.4% (43/9876) of Ashkenazi Jewish chromosomes, including 1 homozygote, by … (more) The p.Thr630Ile variant in BRCA2 is classified as benign because it has been identified in 0.4% (43/9876) of Ashkenazi Jewish chromosomes, including 1 homozygote, by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1. (less)
Likely benign (Jul 15, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000910579.1 First in ClinVar: May 20, 2019 Last updated: May 20, 2019
Likely benign (Sep 19, 2014)	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015)) Method: literature only	Breast-ovarian cancer, familial 2 (Autosomal dominant inheritance) Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000220713.2 First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022	Publications: PubMed (7) PubMed: 12161607‚ 22703879‚ 17924331‚ 20104584‚ 17250666‚ 21990134‚ 20960228
Benign (Jul 07, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: yes Allele origin: germline	KCCC/NGS Laboratory, Kuwait Cancer Control Center Accession: SCV004016892.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023
Likely benign (Apr 27, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast and/or ovarian cancer Affected status: unknown Allele origin: germline	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Accession: SCV004240297.1 First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024
Benign (Aug 22, 2016)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000694581.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013	Publications: PubMed (12) PubMed: 12161607‚ 23231788‚ 20960228‚ 17250666‚ 21990134‚ 21520273‚ 18403564‚ 17924331‚ 22703879‚ 18284688‚ 24323938‚ 20104584 Comment: Variant summary: The BRCA2 c.1889C>T (p.Thr630Ile) variant causes a missense change involving a non-conserved nucleotide with 3/5 in silico tools predict a damaging outcome, although … (more) Variant summary: The BRCA2 c.1889C>T (p.Thr630Ile) variant causes a missense change involving a non-conserved nucleotide with 3/5 in silico tools predict a damaging outcome, although these predictions have yet to be functionally assessed. The variant of interest was found in the large, broad control population, ExAC, with an allele frequency of 21/116384 (1/5543), which does not exceed the estimated maximal expected allele frequency for a pathogenic BRCA2 variant of 1/1333. Multiple publications have cited the variant in affected individuals, in particular, reputable databases have cited the variant to co-occur with multiple pathogenic BRCA2 variants, 1 - c.6468_6469delTC (p.Gln2157IlefsX18), 2 - c.4829_4830delTG (p.Val1610fs), 1 - c.276dupA (p.Gln92fs), and BRCA1 variants, 1 - c.4936delG (Val1646fs), 1 - c.3700_3704delGTAAA (p.Val1234fs), c.5263dupC (p.Ser1755fs). In additional, multiple reputable databases/clinical laboratories and publications cite the variant as "likely benign/benign." Therefore, the variant of interest has been classified as Benign. (less)
Likely benign (Oct 25, 2017)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000210571.9 First in ClinVar: Feb 24, 2015 Last updated: Dec 19, 2017	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (Jan 19, 2021)	criteria provided, single submitter (Sema4 Curation Guidelines) Method: curation	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Sema4, Sema4 Accession: SCV002533272.1 First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Benign (Feb 06, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV004242849.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024
Benign (Nov 19, 2014)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000212902.6 First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Likely benign (Jun 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001961398.20 First in ClinVar: Oct 08, 2021 Last updated: Oct 20, 2024	Comment: BRCA2: BP4 Number of individuals with the variant: 11
variant of unknown significance (Jul 13, 2012)	no assertion criteria provided Method: research	not provided Affected status: no Allele origin: germline	Biesecker Lab/Clinical Genomics Section, National Institutes of Health Study: ClinSeq Accession: SCV000043200.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013	Publications: PubMed (1) PubMed: 22703879 Comment: Converted during submission to Uncertain significance. Number of individuals with the variant: 1 Comment on evidence: The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more) The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
Uncertain significance (May 29, 2002)	no assertion criteria provided Method: clinical testing	Breast-ovarian cancer, familial 2 Affected status: yes Allele origin: germline	Breast Cancer Information Core (BIC) (BRCA2) Accession: SCV000145972.1 First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014	Observation 1: Number of individuals with the variant: 8 Observation 2: Number of individuals with the variant: 1 Geographic origin: Ashkenazi, Western European Observation 3: Number of individuals with the variant: 16 Ethnicity/Population group: Ashkenazi Observation 4: Number of individuals with the variant: 1 Ethnicity/Population group: Asian Observation 5: Number of individuals with the variant: 1 Ethnicity/Population group: Austrian Observation 6: Number of individuals with the variant: 4 Ethnicity/Population group: Western European
Likely benign (Feb 28, 2018)	no assertion criteria provided Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000778649.1 First in ClinVar: May 30, 2018 Last updated: May 30, 2018
Benign (-)	no assertion criteria provided Method: clinical testing	Breast and/or ovarian cancer Affected status: unknown Allele origin: germline	Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research Study: The Canadian Open Genetics Repository (COGR) Accession: SCV000863664.1 First in ClinVar: Dec 24, 2018 Last updated: Dec 24, 2018
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: unknown	Department of Pathology and Laboratory Medicine, Sinai Health System Additional submitter: Franklin by Genoox Study: The Canadian Open Genetics Repository (COGR) Accession: SCV000591778.2 First in ClinVar: Mar 08, 2017 Last updated: Apr 13, 2021	Number of individuals with the variant: 2
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV002035472.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV002038185.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021
Uncertain significance (Dec 19, 2006)	no assertion criteria provided Method: clinical testing	Breast-ovarian cancer, familial 2 Affected status: not provided Allele origin: germline	Sharing Clinical Reports Project (SCRP) Accession: SCV000053954.5 First in ClinVar: Apr 04, 2013 Last updated: Sep 29, 2015
Likely benign (Dec 01, 2017)	no assertion criteria provided Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	True Health Diagnostics Accession: SCV000787920.1 First in ClinVar: Mar 24, 2015 Last updated: Mar 24, 2015
Benign (Oct 03, 2019)	no assertion criteria provided Method: clinical testing	BRCA2-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004740221.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

Comment:

The p.Thr630Ile variant in BRCA2 is classified as benign because it has been identified in 0.4% (43/9876) of Ashkenazi Jewish chromosomes, including 1 homozygote, by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1.

Comment:

Variant summary: The BRCA2 c.1889C>T (p.Thr630Ile) variant causes a missense change involving a non-conserved nucleotide with 3/5 in silico tools predict a damaging outcome, although these predictions have yet to be functionally assessed. The variant of interest was found in the large, broad control population, ExAC, with an allele frequency of 21/116384 (1/5543), which does not exceed the estimated maximal expected allele frequency for a pathogenic BRCA2 variant of 1/1333. Multiple publications have cited the variant in affected individuals, in particular, reputable databases have cited the variant to co-occur with multiple pathogenic BRCA2 variants, 1 - c.6468_6469delTC (p.Gln2157IlefsX18), 2 - c.4829_4830delTG (p.Val1610fs), 1 - c.276dupA (p.Gln92fs), and BRCA1 variants, 1 - c.4936delG (Val1646fs), 1 - c.3700_3704delGTAAA (p.Val1234fs), c.5263dupC (p.Ser1755fs). In additional, multiple reputable databases/clinical laboratories and publications cite the variant as "likely benign/benign." Therefore, the variant of interest has been classified as Benign.

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Functional assays for analysis of variants of uncertain significance in BRCA2.	Guidugli L	Human mutation	2014	PMID: 24323938
Variants of uncertain significance in BRCA1 and BRCA2 assessment of in silico analysis and a proposal for communication in genetic counselling.	Moghadasi S	Journal of medical genetics	2013	PMID: 23231788
Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes.	Johnston JJ	American journal of human genetics	2012	PMID: 22703879
A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS).	Lindor NM	Human mutation	2012	PMID: 21990134
Assessment of rare BRCA1 and BRCA2 variants of unknown significance using hierarchical modeling.	Capanu M	Genetic epidemiology	2011	PMID: 21520273
Germline mutations in BRCA1 and BRCA2 genes in ethnically diverse high risk families in Israel.	Laitman Y	Breast cancer research and treatment	2011	PMID: 20960228
Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.	Borg A	Human mutation	2010	PMID: 20104584
Rapid and sensitive detection of BRCA1/2 mutations in a diagnostic setting: comparison of two high-resolution melting platforms.	De Leeneer K	Clinical chemistry	2008	PMID: 18403564
Evaluation of unclassified variants in the breast cancer susceptibility genes BRCA1 and BRCA2 using five methods: results from a population-based study of young breast cancer patients.	Lee E	Breast cancer research : BCR	2008	PMID: 18284688
A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes.	Easton DF	American journal of human genetics	2007	PMID: 17924331
Contribution of BRCA1 and BRCA2 germline mutations to the incidence of early-onset breast cancer in Cyprus.	Loizidou M	Clinical genetics	2007	PMID: 17250666
Incidence of non-founder BRCA1 and BRCA2 mutations in high risk Ashkenazi breast and ovarian cancer families.	Kauff ND	Journal of medical genetics	2002	PMID: 12161607
The breast cancer information core: database design, structure, and scope.	Szabo C	Human mutation	2000	PMID: 10923033
http://hci-exlovd.hci.utah.edu/variants.php?select_db=BRCA2&action=search_all&search_Variant%2FDNA=c.1889C%3ET	-	-	-	-
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Text-mined citations for rs80358479 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NM_000059.4(BRCA2):c.1889C>T (p.Thr630Ile)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs80358479 ...